MicroRNA-339 inhibits human hepatocellular carcinoma proliferation and invasion via targeting ZNF689

Drug Des Devel Ther. 2019 Jan 22;13:435-445. doi: 10.2147/DDDT.S186352. eCollection 2019.

Abstract

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide, however, the prognosis for HCC remains unsatisfactory. This study aimed to explore the role of miR-339-5p in HCC.

Methods: We first used quantitative real-time PCR to examine the level of miR-339-5p in HCC tissues. Then we further adopted Western blotting assay, CCK8, cell invasion assays, apoptosis detection assay, and luciferase assay to analyze how it mediate the development of HCC.

Results: We found that miR-339 is significantly decreased in primary HCC tissues. Overexpression of miR-339 in HCC cells remarkably suppressed proliferation and invasion and induced apoptosis. However, silencing miR-339 in HCC cells promoted proliferation and invasion, and reduced apoptosis. Moreover, we demonstrated that ZNF689 is a target of miR-339 and there is a negative correlation between miR-339 and ZNF689 expression in the HCC tissues. Overexpression of ZNF689 in miR-339-overexpressing HCC cells partially antagonized the inhibitory effects of miR-339.

Conclusion: Our study revealed that miR-339 inhibits HCC growth through targeting oncoprotein ZNF689 and restoration of miR-339 might be feasible therapeutic strategy for HCC treatment.

Keywords: HCC; ZNF689; miR-339-5p; proliferation; treatment.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / antagonists & inhibitors*
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / pharmacology*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control*
  • Real-Time Polymerase Chain Reaction
  • Structure-Activity Relationship
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured

Substances

  • Apoptosis Regulatory Proteins
  • MIRN339 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • ZNF689 protein, human